Effects of bosentan on right ventricular hypertrophy and connexin43 in rats with chronic hypoxic pulmonary hypertension

AIM: To study the effects of bosentan on right ventricular hypertrophy and connexin43 in rats with chronic hypoxic pulmonary hypertension (HPH). METHODS: Twenty four rats were randomly divided into four groups: control group, bosentan group, placebo group and HPH group. Rats in the control group were in a normal environment for 6 weeks. Rats in the other groups were kept in a hypobaric chamber that simulated the 5 000 m altitude for 8 h/day for 6 weeks. For placebo group and bosentan group, sodium chloride or bosentan was given for 3 weeks starting from the fourth week. At the end of the 6 weeks, pulmonary arterial pressure (PAP) and right ventricular systolic pressure (RVSP) were determined, RV/LV+S and the weight ratio of the right ventricle weight vs. body weight (RW/BW) were calculated. Right ventricle tissues were Masson stained to observe the degree of myocardial fibrosis. Expression of connexin43 was detected by immunohistochemistry and Western blot. Levels of NO and ET-1 in plasma were measured. RESULTS: PAP and RVSP significantly decreased in bosentan group compared with HPH group (P<0.05). The development of the RV/LV+S and RW/BW was significantly prevented in the bosentan group. Masson stain showed that the degree of myocardial fibrosis significantly decreased in bosentan group compared with HPH group (P<0.05). Level of ET-1 and NO in plasma significantly increased in bosentan group compared with that in HPH group (P<0.05). Expression of connexin43 significantly increased in the bosentan group compared with HPH group (P<0.05). CONCLUSION: Bosentan effectively decreases pulmonary artery pressure and restrains right ventricular hypertrophy and remodeling of connexin43.